(1) Field of the Invention
This invention relates to a new microbiological process for preparing the known aminoglycoside antibiotics apramycin, nebramycin factor V' and tobramycin.
(2) Description of the Prior Art
Nebramycin complex is a known complex of eight different aminoglycoside antibiotic components (nebramycin factors I, I', II, III, IV, V', VI and VII) which has been prepared by fermentation of Streptomyces tenebrarius (American Type Culture Collection-- A.T.C.C. 17920 and 17921). The complex and its preparation using the above organism is described in Antimicrob. Agents and Chemother., 1967, pg. 314-348 and in U.S. Pat. No. 3,691,279 (see also U.S. Pat. No. 3,853,709 disclosing preparation of nebramycin factors II and VII by fermentation of Streptomyces tenebrarius NRRL 3816, a mutant strain of Streptomyces tenebrarius A.T.C.C. 17920.
Nebramycin factor VI, now named tobramycin, is reported in Antimicrob. Agents and Chemother., 1970, pg. 309-313 to have the structure ##STR1## Tobramycin is a commercially available antibiotic which possesses a broad spectrum of antimicrobial activity, including activity against Pseudomonas and Proteus microorganisms. K. F. Koch, et al. in J. Antibiotics, 1973, pg. 745-751 state that tobramycin is not produced directly by fermentation of Streptomyces tenebrarius but arises from the acid or base catalyzed hydrolysis of nebramycin factor V' (6"-O-carbamoyltobramycin).
Nebramycin factor II, now named apramycin, is reported in Annual Reports in Medicinal Chemistry, Vol. 9, 1974, pg. 99 to have the structure ##STR2## Apramycin is described as being useful as an antimicrobial agent in treating various plant and animal diseases (see U.S. Pat. Nos. 3,691,279, 3,853,709 and 3,876,767).
Nebramine (also called 3'-deoxyneamine or 3'-deoxyneomycin-A) is an aminoglycoside antibiotic which has been prepared by hydrolysis of tobramycin (Antimicrob. Agents and Chemother., 1970, pg. 309-313). The physical and biological properties of nebramine are disclosed in Belgian Patent 808,393 and in J. Amer. Chem. Soc., Vol. 96, 1974, pg. 3,300-3,305.
Neamine, an aminoglycoside antibiotic degradation product of neomycin, is disclosed in J. Amer. Chem. Soc., Vol. 73, 1951, pg. 2794-2797.
Nebramycin factors IV and V' have been identified as 6"-O-carbamoylkanamycin B and 6"-O-carbamoyltobramycin, respectively. J. Antibiotics, Vol. 26, 1973, pg. 745-751.